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Published on: May 16, 2012
MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer
Mamoun Ahram1, Bayan Abu Alragheb2, Hassan Abushukair3
1Department of Physiology and Biochemistry, School of Medicine, The University of Jordan, Amman 11942, Jordan.
Abstract:
It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC.
Insights
Researchers identified key microRNAs (miRNAs) linked to androgen receptor (AR) activity in triple-negative breast cancer (TNBC). These findings highlight potential new biomarkers and therapeutic targets for TNBC by understanding AR
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel biomarker and therapeutic target identification.
- The androgen receptor (AR) plays a regulatory role in TNBC, partly mediated by microRNAs (miRNAs).
Purpose of the Study:
- To investigate the relationship between AR expression, miRNA profiles, and metastatic potential in TNBC.
- To identify specific miRNAs and signaling pathways influenced by AR in TNBC.
Main Methods:
- Utilized PCR arrays to profile 84 miRNAs in 24 TNBC tissue samples stratified by AR expression and metastasis.
- Employed bioinformatics tools for target prediction and pathway analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).
Main Results:
- Seven miRNAs, including miR-328-3p and miR-489-3p, showed significantly higher expression associated with AR expression.
- miR-205-3p expression was significantly linked to metastasis in TNBC.
- Differential miRNA expression was observed in AR-positive tumors based on metastatic status, implicating roles in transcription regulation and TGF-beta signaling.
Conclusions:
- AR influences TNBC progression through specific miRNA expression patterns.
- Identified miRNAs and pathways (e.g., TGF-beta, kinase-dependent) offer potential as biomarkers and therapeutic targets for TNBC.
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